ENDOPERASITICIDES AGENTS. FIELD OF THE INVENTION The present invention relates to transdermal application agents. containing cyclic depsipeptides, their preparation and their use for the control of endoparasites. Description of the Prior Art A cyclic depsipeptide PF1022 and its effect against endoparasites is known from EP-A 382 173. Other cyclic depsipeptides and their endoparasiticidal effect are the subject of German patent applications DE-A 4 317 432.9; DE-A 4 317 457.4; DE-A 4 317 458.2. In the specification of the patent US 3 004 894 agents containing antibiotic active substances for use by injection are described. These agents therefore differ essentially from the agents according to the invention. Patent reinforcers for transdermal penetration are described in patent application EP-A 0 268 460. However, these products are not suitable as solvents for depsipeptides and can therefore be considered as surfactant additives for transdermal agents at most. However, the level of activity and / or duration of the activity of the previously known agents, especially against certain organisms and / or at low concentrations of application, are not completely satisfactory for all fields of application. Due to the multiple requirements for modern medicines, for example in terms of the level of activity, the duration of the activity, the spectrum of activity, the spectrum of application, toxicity,
REF: 140958
combination of active products, the combination with auxiliary agents of the formulation and due to the possible appearance of resistances, the development of new medicines can never be considered as concluded and there is permanently a great need for new agents, which provide advantages at least in partial aspects against the known agents. In order to enable the animal breeder an application of endoparasiticide active products as simply as possible, it is also desirable to make available a transdermal application agent. As is known from the literature, molecules with molecular weights > 1000 u have an extraordinarily bad penetration through the skin when applied topically. Peptides or proteins with large molecular weights have a particularly poor penetration (Cevc et al, Exp. Opin, Invest Drugs 1997, 6, 12, Pharmazeutische Technologie, Bauer, Fromming, Führer, 1993, page 364, Thieme Verlag, Gurny, Teubner , Dermal and Transdermal Drug Delivery, 1993, page 131, Wissenschaftliche Verlagsgesellschaft). However, penetration is a precondition in the case of endoparasiticide active products since they must be active against endoparasites in the gastrointestinal tract. DETAILED DESCRIPTION OF THE INVENTION The object of the present invention are endoparasiticidal agents, topically and transdermally applied, containing cyclic depsipeptides, constituted by amino acids and by hydroxycarboxylic acids as components, and with 6 to 30 atoms in the ring or in the chain. Surprisingly it has now been found that the depsipeptides mentioned above (with molecular weights> 1000 u, when applied topically in the form of the agents according to the invention, present in animals, such as
for example dogs or cats, a complete pharmaceutical activity. It was also surprising that the depsipeptides showed a long-term stability in the agents according to the invention, whereas in the known topical formulations (such as those described for example in EP-A-0 682 869) an extremely rapid degradation is observed . In addition, the agents according to the invention exhibit, in contrast to what occurs in the case of the known agents, a complete biological activity. The object of the present invention are: 1. Agents containing cyclic depsipeptides alone or in mixture with other active products, characterized in that they contain a solvent or a mixture of solvents and these agents are suitable for topical application in animals. 2. Agents according to item 1, characterized in that they contain 1,2-isopropylidene glycerin. 3. Agents according to item 1, characterized in that they contain 1,2-isopropylidene glycerine as well as benzyl alcohol and / or propylene glycol diacetate. 4. Agents according to claim 1, characterized in that they contain benzyl alcohol and propylene glycol diacetate. The object of the present invention is also the manufacture of endoparasiticidal agents, topically applicable, containing cyclic depsipeptides, consisting of amino acids and hydroxycarboxylic acids as ring components and with 6 to 30 atoms in the ring or in the chain. Preferred cyclic depsipeptides are those with 18 to 24 ring atoms, especially with 24 ring atoms. To the depsipeptides with 18 atoms in the ring belong compounds of the
general formula (I):
wherein R1, RJ and R5 signify, independently of each other, hydrogen, straight chain or branched chain alkyl with up to 8 carbon atoms, hydroxyalkyl, alkanoylalkoxyalkyl, alkoxyalkyl, aryloxyalkyl, mercaptoalkyl, alkylthioalkyl, alkylsulfamylalkyl, alkylsulfonylalkyl, carboxy -alkyl, alkoxycarbonylalkyl, arylalkoxycarbonylalkyl, carbamoylalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, guanidinoalkyl which may optionally be substituted by one or two benzyloxycarbonyl residues or by one, two, three or four alkyl, alkoxycarbonylaminoalkyl, 9-fluorenylmethoxycarbonyl (Fmoc) moieties aminoalkyl, alkenyl, cycloalkyl, cycloalkylalkyl and optionally substituted arylalkyl, halogen, hydroxy, alkyl and alkoxy being mentioned as substituents, R2, R4 and R6 mean, independently of each other, hydrogen, straight-chain or branched-chain alkyl with up to 8 carbon atoms, hydroxyalkyl, me rcaptoalkyl, alkanoyloxyalkyl, alkoxyalkyl, aryloxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, arylalkoxycarbonylalkyl, carbamoyl-alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl,
alkoxycarbonylaminoalkyl. alkenyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl optionally substituted, halogen, hydroxy being mentioned as substituents. alkyl, alkoxy, as well as their optical isomers and racemates. The compounds of the formula (I) are preferred
wherein R1, RJ and R5 mean, independently of each other, straight chain or branched chain alkyl with 1 to 8 carbon atoms, especially methyl, ethyl,
propyl, isopropyl, butyl, isobutyl, sec.-butyl, tere-butyl, pentyl, isopentyl, sec.-pentyl, hexyl, isohexyl, sec.-hexyl, heptyl, isoheptyl, sec.-heptyl, tert.-heptyl, octyl , isooctyl, sec.-octyl, hydroxy-alkyl having 1 to 6 carbon atoms, especially hydroxymethyl, 1-hydroxyethyl, alkanoyloxy with 1 to 4 carbon atoms-alkyl having 1 to 6 carbon atoms,
Especially acetoxymethyl, 1-acetoxyethyl, C 1 -C 4 -alkoxy-C 1 -C 6 -alkyl, especially methoxymethyl, 1-methoxyethyl, arylalkyloxy with 1 to 4 carbon atoms-alkyl with 1 a 6 carbon atoms, especially benzyloxymethyl, 1-benzyloxy-ethyl, n-mercapto-alkyl having 1 to 6 carbon atoms, especially mercaptomethyl, alkylthio having 1 to 4 carbon atoms-alkyl with 1 to 6
carbon atoms, especially methylthioethyl, alkylsulfinyl with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially methylsulphilethyl, alkylsulfonyl with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially methylsulfonylethyl, carboxy -alkyl with 1 to 6 carbon atoms, especially carboxymethyl, carboxyethyl, alkoxycarbonyl with 1 to 4 carbon atoms-alkyl having 1 to 6 carbon atoms, especially methoxycarbonylmethyl, ethoxycarbonylethyl, arylalkoxycarbonyl with 1 to 4 carbon atoms-alkyl with 1 to 6 carbon atoms, especially benzyloxycarbonylmethyl, carbamoyl-C 1 -C 6 alkyl, especially carbamoylmethyl, carbamoylethyl, aminoalkyl with 1 to 6 carbon atoms, especially aminopropyl, aminobutyl, alkylamino with 1 to 4 carbon atoms-alkyl with 1 to 6 carbon atoms, especially methylaminopropyl, methylaminobutyl, dialkylamino with 1 to 4 carbon atoms-alkyl with 1 to 6 carbon atoms, especially dimethylaminopropyl, dimethylaminobutyl, guanidino-C 1 -C 6 -alkyl, especially guanidinopropyl, alkoxycarbonylamino with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially tert-butoxycarbonylaminopropyl, tert. -butoxycarbonylaminobutyl, 9-fluorenylmethoxycarbonyl (Fmoc) amino-C1-C6 alkyl, especially 9-fluorenyl-methoxycarbonyl (Fmoc) aminopropyl, 9-fluorenylmethoxycarbonyl (Fmoc) aminobutyl, alkenyl with 2 to 8 carbon atoms, especially vinyl , allyl, butenyl, cycloalkyl with 3 to 7 carbon atoms, especially cyclopentyl, cyclohexyl, cycloheptyl, cycloalkyl with 3 to 7 carbon atoms-alkyl having 1 to 4 carbon atoms, especially cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, phenyl-alkyl with 1 to 4 carbon atoms, especially
phenylmethyl which may be substituted, if appropriate, by radicals consisting of halogen, especially fluorine, chlorine, bromine or iodine, hydroxy. C 1 -C 4 -alkoxy, especially methoxy or ethoxy, C 1 -C 4 -alkyl, especially methyl, R 2, R 4 and R signify, independently of each other, straight-chain or branched-chain alkyl with 1 to 8 atoms carbon, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl, tere-butyl, pentyl, isopentyl, sec.-pentyl, hexyl, isohexyl, sec.-hexyl, heptyl, isoheptyl, sec-heptyl , tert.-heptyl, octyl, isooctyl, sec.-octyl, hydroxy-C 1-6 -alkyl, especially hydroxymethyl, 1-hydroxyethyl, C 1-4 -alkanoyloxy-C 1-6 -alkyl , especially acetoxymethyl, 1-acetoxyethyl, C 1 -C 4 -alkoxy-C 1 -C 6 -alkyl, especially methoxymethyl, 1-methoxyethyl, arylalkyloxy with 1 to 4 carbon atoms-alkyl with 1 to 6 atoms of carbon, especially benzyloxymethyl, 1-benzyloxy-ethyl, mercapto-alkyl with 1 to 6 atoms carbon atoms, especially mercaptomethyl, alkylthio having 1 to 4 carbon atoms-alkyl having 1 to 6 carbon atoms, especially methylthioethyl, alkylsulfinyl having 1 to 4 carbon atoms-alkyl having 1 to 3 carbon atoms, especially methylsulfinylethyl, alkylsulfonyl with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially methylsulfonylethyl, carboxyC 1 -C 6 -alkyl, especially carboxymethyl, carboxyethyl, alkoxycarbonyl with 1 to 4 carbon atoms-alkyl with 1 to 6 carbon atoms, especially methoxycarbonylmethyl, ethoxycarbonylethyl, arylalkoxycarbonyl having 1 to 4 carbon atoms-alkyl having 1 to 6 carbon atoms, especially benzyloxycarbonylmethyl, carbamoyl-alkyl with 1 to 6 carbon atoms
carbon atoms, especially carbamoylmethyl, carbamoylethyl, aminoalkyl with 1 to 6 carbon atoms, especially aminopropyl, aminobutyl, alkylamino with 1 to 4 carbon atoms-alkyl having 1 to 6 carbon atoms, especially methylaminopropyl, methylaminobutyl, dialkylamino with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially dimethylaminopropyl, dimethylaminobutyl, alkenyl with 2 to 8 carbon atoms, especially vinyl, allyl, butenyl, cycloalkyl with 3 to 7 carbon atoms, especially cyclopentyl, cyclohexyl, cycloheptyl , C3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, especially cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, phenyl, phenyl-C 1 -C 4 -alkyl, especially phenylmethyl, which may be substituted, if appropriate, by residues of the series consisting of halogen, especially fluorine, chlorine, bromine or iodine, hydroxy, alkoxy with 1 to 4 carbon atoms, especially methoxy or ethoxy, alkyl having 1 to 4 carbon atoms, especially methyl, as well as their optical isomers and racemates. Particularly preferred are compounds of the formula (I), in which R1, RJ and R5 mean, independently of one another, straight-chain or branched-chain alkyl with 1 to 8 carbon atoms, especially methyl, ethyl, propyl, isopropyl , butyl, isobutyl, sec.-butyl, pentyl, isopentyl, sec-pentyl, hexyl, isohexyl, sec.-hexyl, heptyl, isoheptyl, sec.-heptyl, octyl, isooctyl, sec.-octyl, hydroxyalkyl, to 6 carbon atoms, especially hydroxymethyl, 1-hydroxyethyl, C 1-4 -alkanoyloxy-C 1-6 -alkyl, especially acetoxymethyl, 1- acetoxyethyl, C 1-4 -alkoxy-alkyl with 1 to 6 carbon atoms, especially methoxymethyl, 1-methoxyethyl, arylalkyloxy with 1 to 4
carbon atoms-C 1 -C 6 -alkyl, especially benzyloxymethyl, 1-benzyloxyethyl, alkoxycarbonylamino with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially tert-butoxycarbonylaminopropyl, tert-butoxycarbonylaminobutyl, alkenyl with 2 to 8 carbon atoms, especially vinyl, allyl, cycloalkyl with 3 to 7 carbon atoms, especially cyclopentyl, cyclohexyl, cycloheptyl, cycloalkyl with 3 to 7 carbon atoms-alkyl with 1 to 4 carbon atoms, especially cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, phenylalkyl with 1 to 4 carbon atoms, especially phenylmethyl, which may be substituted if appropriate by one or more residues identical or different from those mentioned above, R2, R4 and R6 mean, independently of one another, straight chain or branched chain alkyl with 1 to 8 carbon atoms, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl, tere-butyl, pentyl, isopentyl, sec. -pentyl, hexyl, isohexyl, sec.-hexyl, heptyl, isoheptyl, sec-heptyl, tert.-heptyl, octyl, isooctyl, sec.-octyl, hydroxy-alkyl with 1 to 6 carbon atoms, especially hydroxymethyl, aryl- C 1 -C 4 -alkyloxy-C 1 -C 6 -alkyl, especially benzyloxymethyl, 1-benzyloxyethyl, carboxy-C 1 -C 6 -alkyl, especially carboxymethyl, carboxyethyl, alkoxycarbonyl with 1 to 4 carbon atoms- C 1 -C 6 -alkyl, especially methoxycarbonylmethyl, ethoxycarbonylethyl, arylalkoxycarbonyl with 1 to 4 carbon atoms-C 1 -C 6 -alkyl, especially benzyloxycarbonylmethyl, C 1 -C 4 -alkylamino-alkyl with 1 to 6 atoms of carbon, especially methylaminopropyl, methylaminobutyl, dialkylamino with 1 to 4 carbon atoms-alkyl with 1 to 6 atoms
carbon, especially dimethylaminopropyl, dimethylaminobutyl, alkenyl with 2 to 8 carbon atoms, especially vinyl, allyl, butenyl, cycloalkyl with 3 to 7 carbon atoms, especially cyclopentyl, cyclohexyl, cycloheptyl, cycloalkyl with 3 to 7 carbon atoms - alkyl with 1 to 4 carbon atoms, especially cyclopentylmethyl, cyclohexylmethyl, cycloheptyl-methyl, phenyl, phenyl-C 1 -C 4 -alkyl, especially phenylmethyl, which may be substituted, if appropriate, by one or more residues which are the same or different from those above indicated, as well as their optical isomers and racemates. The compounds of the formula (I), in which R1, are very particularly preferred. R3 and R5 mean, independently of one another, straight chain or branched chain alkyl with 1 to 8 carbon atoms, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl, pentyl, isopentyl, seepentyl , hexyl, isohexyl, sec. -hexyl, heptyl, isoheptyl, sec. heptyl, octyl, isooctyl, sec.-octyl, alkenyl with 2 to 8 carbon atoms, especially allyl, cycloalkyl with 3 to 7 carbon atoms-alkyl having 1 to 4 carbon atoms, especially cyclohexylmethyl, phenyl-alkyl with 1 to 4 carbon atoms, especially phenylmethyl, R 2, R 4 and R 6 mean, independently of each other, straight chain or branched chain alkyl with 1 to 8 carbon atoms, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, -butyl, pentyl, isopentyl, sec-pentyl, hexyl, isohexyl, sec.-hexyl, heptyl, isoheptyl, see-heptyl, octyl, isooctyl, sec.-octyl, alkenyl with 2 to 8 carbon atoms, especially vinyl, allyl , C3-C7-C7-C3-C3alkyl-alkyl, especially cyclohexylmethyl, phenyl-alkyl with 1 to 4 carbon atoms
carbon. especially phenylmethyl which may be substituted, if appropriate, by one or more residues which are the same or different from those mentioned above, as well as their optical isomers and racemates. For the purposes of the present invention, all compounds of the general formula (I) which can be present in optically active forms, stereoisomers or in the form of racemic mixtures can be used. However, the optically active, stereoisomeric forms of the compounds of the general formula (I) are preferably used. In particular, the following compounds of the general formula (I) may be mentioned, in which the radicals R1 to R have the following meaning:
Me = Methyl; Phe = Phenyl; Cyclohexyl = cyclohexyl. In addition, the compound PF 1022 known from EP-OS 382 173 of the following formula can be cited as depsipeptides:
In addition, the compound known from the PCT application WO 93/19053 should be cited as depsipeptide. In particular, the compounds of WO 93/19053 of the following formula should be mentioned:
wherein Z means N-morpholinyl, amino, mono- or dimethylamino. In turn, among these, the bis-morpholino derivative (Z = N-morpholinyl) is particularly preferred. In addition, the compounds of the following formula must be mentioned:
wherein R, R ~, RJ, R mean, independently of each other, hydrogen, alkyl with
1 to 10 carbon atoms or aryl, especially phenyl, which are substituted
if appropriate by hydroxy, by alkoxy with 1 to 10 carbon atoms or by halogen. The compounds of the general formula (I) are known and can be obtained according to the processes described in EP-A-382 173, DE-A 4 317 432, DE-A 4 317 457, DE-A 4 317 458, EP- A-634 408, EP-A-718 293, EP-A-872 481, EP-A-685 469, EP-A-626 375, EP-A-664 297, EP-A-669 343, EP-A -787 141, EP-A-865 498, EP-A-903 347. Cyclic depsipeptides with 24 ring atoms also include the compounds of the general formula (Ia)
where Rla, R 2a, R 1a and R 2a mean independently, alkyl having 1 to 8 carbon atoms, haloalkyl with 1 to 8 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, aralkyl, aryl. R a, R 5a, R 7a, R 9a mean, independently of one another, hydrogen or straight chain or branched chain alkyl with 1 to 8 carbon atoms, which may be substituted, if appropriate, by hydroxy, by alkoxy having 1 to 4 carbon atoms,
by carboxy, by O O
(-COH), by carboxamide, by (-O-C-NH2), by
imidazolyl, by indolyl, by guanidino, by -SH or by alkylthio with 1 to 4 carbon atoms and further mean aryl or aralkyl which may be substituted by halogen, by hydroxy, by alkyl with 1 to 4 carbon atoms, by alkoxy with 1 to 4 carbon atoms, R 4a, R 6a, R 8a, R 10a mean, independently of one another, hydrogen, straight-chain alkyl with 1 to 5 carbon atoms, alkenyl with 2 to 6 carbon atoms, cycloalkyl with 3 to 7 carbon atoms carbon, which may be optionally substituted by hydroxy, by alkoxy with 1 to 4 carbon atoms, by carboxy, by carboxamide, by imidazolyl, by indolyl, by guanidino, by SH or by alkylthio with 1 to 4 carbon atoms, as they mean aryl or aralkyl which may be substituted by halogen, by hydroxy, by alkyl with 1 to 4 carbon atoms, by alkoxy with 1 to 4 carbon atoms, as well as their optical isomers and racemates. Preferably, the compounds of the formula (la), in which Rla, R 2a, R 1a and R 12a mean, independently of one another, methyl, ethyl, propyl, isopropyl, n-, s-, t-butyl or phenyl, which it is optionally substituted, for example, by halogen, by alkyl with 1 to 4 carbon atoms, by OH, by alkoxy with 1 to 4 carbon atoms, as well as by means of benzyl or phenyl, which may be substituted, if appropriate, by the radicals which have been substituted. indicated for phenyl;
Rja to R10a have the meaning indicated above. Particularly preferred are compounds of the formula (Ia) in which Rla, R 2a, R 1a and R 12a mean independently of each other. methyl, ethyl, propyl, isopropyl or n-, s-, t-butyl, Rja, R5a, R7a, R9a mean hydrogen, straight chain or branched chain alkyl with 1 to 8 carbon atoms, especially methyl, ethyl, propyl , i-propyl, n-, s-, t-butyl, which may optionally be substituted by alkoxy with 1 to 4 carbon atoms, especially by methoxy, ethoxy, imidazolyl, indolyl or alkylthio having 1 to 4 carbon atoms especially methylthio, ethylthio, furthermore they are phenyl, benzyl or phenethyl, which may be substituted, if appropriate, by halogen, especially chlorine. R4a, R6a, R8a, R10a mean, independently of one another, hydrogen, methyl, ethyl, n-propyl, n-butyl, vinyl, cyclohexyl, which may be substituted, if appropriate, by methoxy, by ethoxy, by imidazolyl, by indolyl, by methylthio, by ethylthio, as well as by means of isopropyl, s-butyl, they also mean phenyl, benzyl or phenylethyl optionally substituted by halogen. The compounds of the formula (la) can also be obtained according to the processes described in EP-A-382 173, DE-A 4 317 432, DE-A 4 317 457, DE-A 4 317 458, EP-A-634 408, EP-A-718 293, EP-A-872 481, EP-A-685 469, EP-A-626 375, EP-A-664 297, EP-A-669 343, EP-A-787 141 , EP-A-865 498, EP-A-903 347. The agents according to the invention are suitable, with a toxicity favorable to warm-blooded animals, for the control against pathogenic endoparasites in man and in the maintenance and breeding of useful animals, breeding, zoo, laboratory, trial and company. In this case they are active against all stages of development or against individual stages of development of pests as well
as against resistant and normally sensitive types. Through the fight against pathogenic endoparasites diseases, death cases and yield losses (for example in the production of meat, milk, wool, skins, eggs, honey, etc.) are reduced, in such a way that, through the use of the active products is possible a more economical and simple maintenance of the animals. Pathogenic endoparasites include cestodes, trematodes, nematodes, acanthocephalic, especially of the order of Pseudophyllidia, for example: Diphyllobothrium spp., Spirometra spp., Schistocephalus spp., Ligule spp., Bothridium spp., Diphlogonoporus spp. From the order of Cyclofilideos for example: Mesocestoides spp., Anoplocephala spp., Paranoplocephala spp., Moniezia spp., Thysanosomsa spp., Thysaniezia spp., Avitellina spp., Stilesia spp., Cittotaenia spp., Andyra spp., Bertiella spp., Taenia spp., Echinococcus spp., Hydatigera spp., Davainea spp., Raillietina spp., Hymenolepsis spp., Echinolepsis spp., Echinocotyle spp., Diorchis spp., Dipylidium spp., Joyeuxiella spp., Diplopylidium spp. From the subclass of the Monogeneans for example: Gyrodactylus spp. ., Dactylogyrus spp., Polystoma spp. From the subclass of the Digéneos, for example: Diplostomum spp., Posthodiplostomum spp., Schistosoma spp., Trichobilharzia spp., Ornithobilharzia spp., Austrobilharzia spp., Gigantobilharzia spp., Leucochloridium spp. ., Brachylaima spp., Echinostoma spp., Echinoparyphium spp., Echinochasmus spp., Hypoderaeum spp., Fasciola spp., Fasciolides spp., Fasciolopsis spp., Cyclocoelum spp., Typhlocoelum spp., Paramphistomum spp., Calicophoron spp., Cotylophoron spp., Gigantocotyle spp., Fischoederius spp., Gastrothyl acus spp., Notocotylus spp., Catatropis spp., Plagiorchis spp., Prosthogonimus spp., Dicrocoelium spp., Eurytrema spp., Troglotrema spp.,
Paragonimus spp., Collyriclum spp., Nanophyetus spp., Opisthorchis spp., Clonorchis spp., Metorchis spp., Heterophyes spp., Metagonimus spp. From the order of Enoplids, for example: Trichuris spp. Capillaria spp., Trichlomosoides spp., Trichinella spp. From the order of the Rhabditios, for example: Micronema spp.,
Strongyloides spp. From the order of Stromelidae, for example: Stronylus spp., Triodontophorus spp., Oesophagodontus spp., Trichonema spp., Gyalocephalus spp., Cylindropharynx spp., Poteriostomum spp., Cyclococercus spp., Cylicostephanus spp., Oesophagostomum spp., Chabertia spp., Stephanurus spp., Ancylostoma spp., Uncinaria spp., Bunostomum spp., Globocephalus spp., Syngamus spp., Cyathostoma spp., Metastrongylus spp., Dictyocaulus spp., Muellerius spp., Protostrongylus spp. , Neostrongylus spp., Cystocaulus spp., Pneumostrongylus spp., Spicocaulus spp., Elaphostrongylus spp., Parelaphostrongylus spp., Crenosoma spp., Paracrenosoma spp., Angiostrongylus spp., Aelurostrongylus spp., Filaroides spp., Parafilaroides spp., Trichostrongylus. spp., Haemonchus spp., Ostertagia spp. Marshallagia spp., Cooperia spp., Nematodirus spp., Hyostrongylus spp., Obeliscoides spp., Amidostomum spp., Ollulanus spp. From the order of the Oxyurids, for example: Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp. ., Aspiculuris spp., Heterakis spp. From the order of the Ascarids, for example: Ascaris spp., Toxascaris spp., Toxocara spp., Parascaris spp., Anisakis spp., Ascaridia spp. From the order of the Spirurids, for example: Gnathostoma spp., Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp.
From the order of the Filiáridos, for example: Stephanofilaria spp., Parafilaria spp. Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia spp., Wuchereria spp., Onchocerca spp. From the order of the Gigantohinquídeos for example: Filicollis spp., Moniliformis spp., Macracanthorhynchus spp., Prosthenorchis spp. To the useful and breeding animals belong mammals such as for example cows, horses, goats, pigs, goats, camels, hippos, donkeys, rabbits, deer, reindeer, animals for the production of fur such as for example mink, chinchillas, raccoons, birds such as for example chickens, geese, ducks, turkeys, freshwater and saltwater fish such as, for example, trouts, carps, eels, reptiles, insects such as, for example, honey bees and silk worms. To the laboratory and test animals belong mice, rats, guinea pigs, golden hamsters, dogs and cats. Pet animals include dogs and cats. The application can be carried out both prophylactically and therapeutically. Suitable solvents are all organic solvents, for example ethanol, diethylene glycol monomethyl ether, dipropylene glycol monomethyl ether, benzyl benzoate, butyl lactate, 1,2-isopropylidene glycerin, benzyl alcohol and propylene glycol diacetate, particularly preferably 1,2-isopropylidene glycerine. , benzyl alcohol and propylene glycol diacetate, individually or as mixtures. The agents according to the invention contain solvents or solvent mixtures in amounts of 95% by weight up to 50% by weight, preferably 95% by weight up to 70% by weight, and particularly preferably 95% by weight up to 80% by weight.
Preference is given to agents according to the invention, which contain at least 60% by weight (based on the total weight of the finished agent), preferably at least 65% by weight, of 1,2-isopropylidene glycerin. Particularly preferably, this agent contains benzyl alcohol, in the form of another solvent, in proportions of up to 40% by weight, preferably from 10 to 30% by weight. In this case the proportion of the solvent will be chosen in such a way that it complements up to 100% with the active product and, if necessary, with the auxiliary products used. It may be advantageous to add to the agents according to the invention other auxiliaries customary in veterinary medicine, such as, for example, thickeners. Examples of thickeners are: inorganic thickeners such as bentonite, colloidal silicic acid, aluminum monostearate, organic thickeners such as cellulose derivatives (especially hydroxypropylcellulose), polyvinyl alcohols and their copolymers, acrylates and methacrylates. In addition, preservatives, especially stabilizers against oxidation, can be used as auxiliary products. Examples are butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and ascorbic acid. The active compounds can also be present in the compositions according to the invention in a mixture with synergists or with other active agents, which act against the pathogenic endoparasites. Such active compounds are, for example, L-2,3,5,6-tetrahydro-6-phenyl-imodazothiazole, benzimidazolecarbamates such as Febantel, in addition
Pyrantel, Praziquantel and Ivermectin. Preparations ready for use contain the active compounds in concentrations of 0.0001 to 25 weight percent, preferably 0.1 to 20 weight percent. The agents are prepared by mixing the components in the corresponding amounts in suitable devices.
In general, it has been found advantageous to administer amounts of the mixture according to the invention from about 1 to about 100 mg of active compound per kg of body weight per day in order to achieve effective results. Preference is given to 1 to 10 mg of active compound per kg of body weight. The following examples explain the invention without limiting it. Example 1. 5 parts by weight of depsipeptides are dissolved in 66.5 parts by weight of isopropylidene glycerin and 28.5 parts by weight of benzyl alcohol under stirring. A clear, colorless solution is formed. Example 2 5 parts by weight of depsipeptide are dissolved in 66.5 parts by weight of propylene glycol diacetate and 28.5 parts by weight of benzyl alcohol under stirring. A clear, colorless solution is formed. Example 3. In a solution of Example 1, 2 parts by weight of hydroxypropylcellulose are further dissolved. Example 4. The solutions of examples 1 or 2 are applied on the skin of the back of animals infected with parasites, at a dose of 5 mg of depsipeptides per kg of body weight. After 2 to 4 days the animals are free of parasites.
Example 5. The solution of Example 3 is applied on the loins of cows infected with Cooperia oncophara at a dose of 5 mg of active product / kg of body weight. The reduction of the vitrologic infection was 99%. It is noted that, in relation to this date, the best known method for the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.